Inactivation of ELF/TGF-β signaling in human gastrointestinal cancer

Varalakshmi Katuri, Yi Tang, Blair Marshall, Asif Rashid, Wilma Jogunoori, Eugene A. Volpe, Anton N. Sidawy, Stephen Evans, Jonathan Blay, G. Ian Gallicano, E. Premkumar Reddy, Lopa Mishra, Bibhuti Mishra

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


TGF-β/Smads regulate a wide variety of biological responses through transcriptional regulation of target genes. ELF, a β-spectrin, plays a key role in the transmission of TGF-β-mediated transcriptional response through Smads. ELF was originally identified as a key protein involved in endodermal stem/progenitor cells committed to foregut lineage. Also, as a major dynamic adaptor and scaffolding protein, ELF is important for the generation of functionally distinct membranes, protein sorting and the development of polarized differentiated epithelial cells. Disruption of elf results in the loss of Smad3/Smad4 activation and, therefore, a disruption of the TGF-β pathway. These observations led us to pursue the function of ELF in gastrointestinal (GI) epithelial cell-cell adhesion and tumor suppression. Here, we show a significant loss of ELF and reduced Smad4 expression in human gastric cancer tissue samples. Also, of the six human gastric cancer cell lines examined, three show deficient ELF expression. Furthermore, we demonstrate the rescue of E-cadherin-dependent homophilic cell-cell adhesion by ectopic expression of full-length elf. Our results suggest that ELF has an essential role in tumor suppression in GI cancers.

Original languageEnglish (US)
Pages (from-to)8012-8024
Number of pages13
Issue number54
StatePublished - Dec 1 2005
Externally publishedYes


  • Cell adhesion
  • E-cadherin
  • ELF
  • Gastric cancer
  • Smad4
  • TGF-β

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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